1. Technical Field
The invention relates to methods and materials involved in aiding implantation of an egg or embryo in the uterus of a female mammal.
2. Background Information
Human in vitro fertilization was initially reported in England around 1978 (see Steptoe and Edwards (1978) Lancet 2:366). Despite its low success rate, in vitro fertilization is generally used as a treatment for infertility as well as for applications involved in selection against genetic diseases. The transfer of more advanced healthy embryos has lead to some improvement in the rate of implantation per embryo (Gardner et al. (1998) Fertility and Sterility 69:84). Improvements in the rate of pregnancy through in vitro fertilization also have been achieved by superovulation and the transfer of multiple embryos (Wortham et al. (1983) Fertility and Sterility 39:785). However, multiple embryo transfers often lead to the generation of multi-fetal pregnancies resulting in obstetrical problems including preterm birth.
The invention provides materials and methods that can be used to aid implantation of an egg or embryo in the uterus of a female mammal. More particularly, the invention provides improved methods for the transfer of eggs and embryos into the uteri of female mammals, as well as methods for adjusting the positions of eggs and embryos in the uteri. The invention also provides eggs and embryos having improved stability in the uteri of mammals and methods for preparing such eggs and embryos. Methods of the invention involve the use of magnetic particles and a magnetic field.
In some embodiments, the invention provides methods for stabilizing mammalian embryos within the uteri of suitable mammals. These methods involve attaching magnetic particles to mammalian embryos to generate coated embryos, transferring the coated embryos into the uteri of suitable mammals, and then applying magnetic fields to the mammals to stabilize the embryos within the uteri. Embryos can be the embryos of humans. Embryos also can be the embryos of horses, cows, or pigs. Embryos can be embryos at the early or late cleavage stage, at the morula stage, or at the blastocyst stage. One embryo can be transferred at a time, or more than one embryo can be transferred simultaneously.
In some embodiments, embryos can have zonae pellucidae to which magnetic particles can be attached. Magnetic particles can be attached to the zonae pellucidae of embryos by reactions with chemical functional groups or through macromolecules such as avidin molecules, streptavidin molecules, protein A molecules, lectin molecules, and antibodies. The zonae pellucidae can have adherent cells through which magnetic particles are attached. Adherent cells can be spermatozoa or cumulus cells such as coronal cells.
The magnetic particles can be paramagnetic particles. The magnetic field can be generated by a permanent magnet or an electromagnet. Permanent magnets or electromagnets can be external or internal to the mammal. The magnetic field generated by an external magnet can be trans-abdominal, trans-sacral, or trans-lumbar to the mammal. The magnetic field generated by an internal magnet can be trans-rectal, trans-urethral, trans bladder, or intra-abdominal to the mammal. The magnetic field can be applied during, after, or during and after transfer of the embryo.
The invention also provides methods for adjusting the locations of coated embryos within the uteri of mammals. These methods involve applying magnetic fields to mammals containing coated embryos. The magnetic fields have sufficient strengths to affect the locations of the coated embryos. The location of an embryo can be adjusted so that the embryo is in proximity of the endometrium or/and at the uterine fundus of a mammal.
In other embodiments, the invention provides methods for preparing embryos having improved stability in the uteri of mammals. These methods involve contacting embryos with magnetic particles capable of attaching to the embryos. The invention also provides for mammalian embryos coated with magnetic particles. Mammalian embryos can be human embryos. Magnetic particles can be paramagnetic particles.
In yet other embodiments, the invention provides methods for stabilizing mammalian eggs within the uteri of suitable mammals. These methods involve attaching magnetic particles to the external zonae pellucidae of the eggs to generate coated eggs, transferring the coated eggs into the uteri, and applying magnetic fields to the mammals to stabilize the eggs within the uteri. In some of these embodiments, eggs can be unfertilized eggs. Eggs can be human eggs. Eggs can be from a horse, a cow, or a pig. One egg can be transferred at a time, or more than one egg can be transferred simultaneously.
Magnetic particles can be attached to the zonae pellucidae of eggs by reactions with chemical functional groups or through macromolecules such as avidin molecules, streptavidin molecules, protein A molecules, lectin molecules, and antibodies. The zonae pellucidae can have adherent cells through which magnetic particles can be attached. Adherent cells can be spermatozoa or cumulus cells such as coronal cells.
The magnetic particles can be paramagnetic particles, and the magnetic field can be generated by a permanent magnet or an electromagnet. Permanent magnets or electromagnets can be external or internal to the mammal. The magnetic field generated by an external magnet can be trans-abdominal, trans-sacral, or trans-lumbar to the mammal. The magnetic field generated by an internal magnet can be trans-rectal, trans-urethral, trans bladder, or intra-abdominal to the mammal. The magnetic field can be applied during, after, or during and after transfer of the egg.
The invention also provides methods for adjusting the locations of coated eggs within the uteri of mammals. These methods involve applying magnetic fields to mammals containing coated eggs. Magnetic fields have sufficient strengths to affect the locations of the coated eggs. The location of an egg can be adjusted so that the egg is in proximity of the endometrium or/and at the uterine fundus of a mammal.
In other embodiments, the invention provides methods for preparing eggs having improved stability in the uteri of mammals. These methods involve contacting eggs with magnetic particles capable of attaching to these eggs. The invention also provides for mammalian eggs coated with magnetic particles. Mammalian eggs can be human eggs. Magnetic particles can be paramagnetic particles.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.